title: Chitosan-dextran sulphate nanocapsule drug delivery system as an effective therapeutic against intraphagosomal pathogen Salmonella.
abstract: OBJECTIVE
  The ability to target conventional drugs efficiently inside cells to kill intraphagosomal bacteria has been a major hurdle in treatment of infective diseases. We aimed to develop an efficient drug delivery system for combating infection caused by Salmonella, a well-known intracellular and intraphagosomal pathogen. Chitosan-dextran sulphate (CD) nanocapsules were assessed for their efficiency in delivering drugs against Salmonella.
  
  
  METHODS
  The CD nanocapsules were prepared using the layer-by-layer method and loaded with ciprofloxacin or ceftriaxone. Antibiotic-loaded nanocapsules were analysed in vitro for their ability to enter epithelial and macrophage cells to kill Salmonella. In vivo pharmacokinetics and organ distribution studies were performed to check the efficiency of the delivery system. The in vivo antibacterial activity of free antibiotic and antibiotic loaded into nanocapsules was tested in a murine salmonellosis model.
  
  
  RESULTS
  In vitro and in vivo experiments showed that this delivery system can be used effectively to clear Salmonella infection. CD nanocapsules were successfully employed for efficient targeting and killing of the intracellular pathogen at a dosage significantly lower than that of the free antibiotic. The increased retention time of ciprofloxacin in the blood and organs when it was delivered by CD nanocapsules compared with the conventional routes of administration may be the reason underlying the requirement for a reduced dosage and frequency of antibiotic administration.
  
  
  CONCLUSIONS
  CD nanocapsules can be used as an efficient drug delivery system to treat intraphagosomal pathogens, especially Salmonella infection. This delivery system might be used effectively for other vacuolar pathogens including Mycobacteria, Brucella and Legionella.
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
authors.forename: Divya Prakash
authors.initials: DP
authors.lastname: Gnanadhas
authors.forename: Midhun
authors.initials: M
authors.lastname: Ben Thomas
authors.forename: Monalisha
authors.initials: M
authors.lastname: Elango
authors.forename: Ashok M
authors.initials: AM
authors.lastname: Raichur
authors.forename: Dipshikha
authors.initials: D
authors.lastname: Chakravortty
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000493:pharmacokinetics; D002460:Cell Line; D048271:Chitosan / Q000378:metabolism* / Q000493:pharmacokinetics; D002939:Ciprofloxacin / Q000378:metabolism* / Q000493:pharmacokinetics; D016264:Dextran Sulfate / Q000378:metabolism* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000008:administration & dosage*; D010588:Phagosomes / Q000378:metabolism / Q000382:microbiology; D012475:Salmonella / Q000187:drug effects*; D012481:Salmonella Infections, Animal / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D053769:Nanocapsules; D002939:Ciprofloxacin; D048271:Chitosan; D016264:Dextran Sulfate
keywords: ciprofloxacin/ceftriaxone/gentamicin; intravacuolar pathogens; layer-by-layer (LbL); polyelectrolyte capsules; typhoid